This study consists of three interrelated projects that examine the regulation of procollagen biosynthesis, the structure of the basement membrane procollagens, and the structure and function of a recently recognized matrix and cell surface protein, fibronectin. We will develop complementary DNA probes to collagen messenger RNAs and antibodies to a number of different collagens in order to determine, in cell culture, whether regulation of messenger RNA levels or translational control is used to modulate collagen biosynthesis under a variety of conditions (viral transformation, developmental programs, feedback inhibition). These methods will also be applied to studies of connective tissue disorders. Cell-free translation will be used to identify transient intracellular precursors of procollagen. We think it likely that procollagens that are commonly found in basement membranes in association with fibronectin, play an important role in the structure of the external protein meshwork, the zone of the extracellular matrix immediately adjacent to the cell surface. Structural domains in fibronectin that are responsible for binding to collagen and to the cell surface will therefore be characterized. We will compare the structure of fibronectin with that of the closely related protein, cold-insoluble globulin, and elucidate the role of these proteins in promoting cell adhesion to a substratum and cell migration, and in conferring a normal morphology and cell-surface characteristics to mesenchymally derived cells.